Innovative molecular microscopy tracks breast cancer spread

The new technique could track which breast cancer cell populations are responsible for the spread of the disease and, for the first time, highlight that the location of cancer cells may be as important
as mutations in tumor growth.

The method was invented by a team from the Wellcome Sanger Institute, EMBL-EBI at EMBL, the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ), the Swedish Life Sciences Laboratory and its collaborators
.
It can be used to help answer some of the big questions in the cancer field, such as why some cancer cells spread, how resistance develops, and why some therapies fail
.

THE NEW STUDY, PUBLISHED TODAY (NOVEMBER 9, 2022) IN NATURE, COMBINES THE GENETIC INFORMATION OF CANCER CELLS, THE TYPES OF CELLS AROUND THEM, AND HOW THEY INTERACT WITH THE ENVIRONMENT OVER TIME TO SHOW HOW IT IS NOW POSSIBLE TO MAP THE DEVELOPMENT OF
TUMORS.
In the future, this approach could be used to see how treatments affect cancer, not only at the genetic level, but also to see how tumors interact
with the immune system and the surrounding environment.

Breast cancer is one of the most common cancers in the UK, around 55500 women and 370 men are diagnosed each year breast cancer usually starts when cells start growing uncontrollably, often due to
cell mutations.
Over time, tumors become a patchwork of cells, called cancer clones, each with a different mutation.

Because of their genetics, they respond differently
to treatment.
For example, some of these cancer cells may become resistant to treatment, or some may spread throughout the body
.

The mutations that occur will be affected
by what happens around the cancer, the cells around the cancer cells, and the individual's immune system.
Therefore, if you can study the environment in which cancer cells are located, what mutations occur, and which cancer cells spread throughout the body, you can fully understand the evolution of tumors
.

Created by researchers and their collaborators from the Wellcome Sanger Institute, EMBL-EBI, DKFZ, and life science laboratories, the new technique uses hundreds of thousands of tiny fluorescent molecular probes to interrogate cellular DNA and RNA and scans large pieces of tissue
using fluorescence microscopy.
It can genetically and physically map cancer's unique set of clones, how their gene expression programs change, and how they interact
with the environment.

Artem Lomakin, lead author of EMBL-EBI and Deutsches Krebsforschungszentrum, DKFZ, said: "We have created a system that combines computational and experimental techniques that allows us to map the evolutionary lineage
of cancer in the natural habitat of human tissue 。 While it has previously been possible to trace the lineage of cancer tumor cells in experimental setups, this is the first time multiple lineages have been traced in human tissues, providing a complete overview
of how breast cancer develops in vivo.
Until now, the insights generated by our systems would not have been possible, especially at
this scale.
”

The team found that there are specific, often unexpected, clonal growth patterns at multiple stages of breast cancer development, and that gene clones behave differently depending on where they start in the breast
.
The findings also show that sometimes it's not just genes that influence cancer growth, but also the location of
tumors.
In this case, genes can be used as a tool to discover more cases of what is going on, driving cancer clones to spread throughout the body
.

Professor Mats Nilsson, co-senior author of Stockholm University's Life Sciences Laboratory, said: "Cancer is caused by genetic mutations in cells and this study is the first time we have been able to use DNA-based specific probes to target dozens of mutations
in a group of cancer cell clones.
This innovative technique allows us to accurately reconstruct the spread
of these clones.
An important insight from our study is that cancer cells may survive and spread for reasons more than just genetic changes; It could also be where
they are.
This adds another layer of complexity, as well as new potential approaches
to the disease.
It could also explain why some treatments only work for certain people, even if they have similar mutations to others because tumors are found
in different areas of the breast.
”

In the future, by influencing the environment around tumors, it is possible to develop therapies
that prevent or reduce the ability of cancer to grow and spread.
In addition to this, researchers can use newly developed tools to test how new treatments affect cancer and how they interact with the immune system, giving a comprehensive understanding of how treatments work and possible side effects
.

Professor Moritz Gerstung, co-senior author from the German Cancer Research Centre (Deutsches Krebsforschungszentrum, DKFZ), said: "Sequencing cancer tumours can give us a better understanding of tumours' genetic diversity
.
But what's exciting about this technology is that for the first time we can see how the environment affects the evolution
of cancer.
Being able to see which cancer clones become more aggressive and which won't will give us a better understanding of the key steps in tumor growth and how we can reduce or prevent disease
.
”

Dr Lucy Yates, co-senior author of the Wellcome Sanger Institute, said: "Our study creates a tool that can track which breast cancer cells cause tumours elsewhere in the body and help answer some of the big questions about cancer, such as why some cancer cells spread and some don't
.
To fully understand and treat breast cancer, we need to be able to see the full picture
of how cancer interacts in the body, with surrounding cells, and with the immune system.
This new technology combines multiple technologies and expertise to do this, bringing together different approaches to provide a comprehensive view of cancer that was not possible before
.
”